Water-soluble salts of dihydro



Patented May 16, 1950 UNITED STATES PATENT OFFICE WATER-SOLUBLE SALTS OFDIHYDRO- ERGOCRISTINE Arthur Stoll and Albert Hofmann, Basel,Switzerland, assignors to Sandoz zerland, a Swiss firm Limited, Basel,Swit- 3 Claims.

The present invention is a continuation-inpart of our co-pending patentapplication, Ser. No. 385,198, filed March 25, 1941, now abandoned,which relates to sympatheticolytically active dihydro-derivatives oflysergic acid amides.

The present invention more particularly relates to the preparation ofwater-soluble salts of dihydro-ergocristine.

Dihydro-ergocristine may be produced by hydrogenating ergocristine underpressure in the presence of a suitable catalyst and of a solvent and, insome cases, at an elevated temperature, the method of production ofdihydro-ergocristine being described in detail in our co-pending patentapplication, Ser. No. 385,198 (of. Example 4 thereof).

The preparation of the dihydro-ergocristine can be carried out byneutralizing a solution or a suspension of dihydro-ergocristine in asuitable solvent with the respective alkyl sulphonic acid. The saltsthus obtained are generally beautifully crystallized compounds which aremore or less soluble in water and which are useful products fortherapeutical purposes, as they are much better soluble in water thanthe dihydro-ergocristine itself.

The following examples, without being limitative, describe the presentinvention.

Example 1 A solution of 6.11 parts by weight of dihydroergocristine /100mol) in 60 parts by volume of methanol is treated with parts by volumeof n-methanolic solution of methane-sulphonic acid. The solution is thenevaporated to dryness in vacuo and the residue dissolved in parts byvolume of acetone. From this solvent the newdihydro-ergocristine-methane-sulphonate crystallizes out in form of finewhite needles which are filtered and, after washing with some acetone,dried in vacuo over calcium chloride. The new compound melts withdecomposition at 230 0. (corn) and possesses, after drying inhigh-vacuo, the formula C35H41O5N5'CH3SO3H. 1 part of the salt issoluble at C. in 400 parts of water, thus yielding stable solutions.

Emample 2 The dihydro-ergocristine ethane-sulphonate water-soluble saltsof can be prepared in analogous manner to that described in Example 1.The new salt melts with decomposition at 215 C. (corn) and possesses theformula C35H4105N5'CH3CH2SO3H. 1 part Of this salt is soluble in 300parts of water at 20 C., thus yielding stable solutions.

What we claim is:

1. The water-soluble alkyl-sulphonic acid salts of dihydro-ergocristineof the formula which compounds beautifully crystallize from an organicsolvent,their crystals melting with decomposition and yielding stableaqueous solu- 15 tions and the same being suitable for therapeuticalpurposes.

2. The water-soluble methane-sulphonic acid salt of dihydro-ergocristineof the formula CasI-LnOsNs CHsSOcH which crystallizes from acetone inform of fine white needles melting with decomposition at 230 C., 1 partof which is soluble at 20 C. in 400 parts of water yielding stablesolutions, and which possesses valuable therapeutical properties.

3. The water-soluble ethane-sulphonlc acid salt of dihydro-ergocristineof the formula CasHnOsNs CHsCHzSOaH 3 which crystallizes from acetone inform of fine white needles melting with decomposition at 215 C. (corn),1 part of which is soluble in 300 parts of water at 20 C. yieldingstable solutions, and which possesses valuable therapeutical properties.

ARTHUR STOLL. ALBERT HOFMANN.

REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS OTHER REFERENCES Helv. Chim. acta, vol. 26 (1943),pp. 1570-1601 and 2070-2081,

1. THE WATER-SOLUBLE ALKYL-SULPHONIC ACID SALTS OF DIHYDRO-ERGOCRISTINEOF THE FORMULA